EXPRESSION OF EXTRACELLULAR-MATRIX PROTEINS AND THE ROLE OF FIBROBLASTS AND MACROPHAGES IN REPAIR PROCESSES IN ISCHEMIC PORCINE MYOCARDIUM

In the experimental model of coronary microembolization in pig hearts, the processes of wound healing and scar formation were studied. Metho ds employed were: electron microscopy, immunohistochemistry using mono clonal antibodies (against fibronectin, laminin, collagen I, III, and VI, chondroitin sulfate, and vimentin), and in situ hybridization with radioactively labeled RNA (histones, fibronectin) or cDNA (acidic fib roblast growth factor) probes. The following time course for expressio n of various proteins and their mRNAs was established: Mitotic activit y was significant at 3 d as well as expression of fibronectin mRNA. Ce llularity comprising blood borne cells and macrophages was high. At 7 d, fibronectin, laminin and collagen VI accumulation were pronounced, vimentin positive cells were numerous. At 4 weeks, collagen expression was prominent, but interstitial cells were still present. It is concl uded that healing after myocardial necrosis passes through the classic al phases of wound healing, i.e., granulation tissue formation and fin al scar formation. Different extracellular matrix proteins show a diff ering time course of expression, tumor necrosis factor-alpha (TNF-alph a) and acidic fibroblast growth factor (aFGF) produced by macrophages may be involved in inflammatory processes and angiogenesis. Scar forma tion is not yet completed at 4 weeks after injury.